Studies on the nature of the cell surface antigen reacting with cytolytic T lymphocytes in murine oncornavirusinduced tumors

Abstract

Laboratoire d'lmmunologie et de Virologie des Tumeurs, INSERM U 152, Hgpital Cochin, ParisThe nature of the target antigen, expressed on murine sarcoma virus (MSV) and related murine tumors which reacts with T killer lymphocytes, remains ill-defined. The experiments reported here show that: (a) the previously described H-2 restriction phenomenon is found under all experimental conditions including 3-4 and 16-20-h chromium release tests. With 16-20 h tests and highly efficient T lymphocytes however, quantitative methods are necessary to demonstrate the H-2 restriction. These results support the hypothesis that H-2 molecules may be determinant in the structure and/or in the function of the cytolytic T lymphocyte (CTL) reactive antigen. (b) Under syngeneic conditions (ie. using H-2-identical immune lymphocytes, stimulators and target cells), the pattern of specificities recognized by anti-MSV or antiFriend T killer cells on 20 different lymphomas suggests that the main reactive antigen is an "FMR-like" substance. Identical conclusions were drawn from competition experiments. (c) Blockings were obtained by pre-incubation of the target cells with a goat anti-gp70, suggesting a possible role of the viral gp70 in the antigen recognized. However, this could be due to nonspecific reactions as two other anti-gp70 sera as well as with antisera directed against the viral componentsgp45, pr60, p30, p15, p12 and p10 did not block. The CTL/tumor cell interaction was not inhibited by virion-associated antigens added to the medium. Lysostrip and co-capping experiments have failed to reveal an association between H-2 and gp70. The nature of the viral protein bearing the "FMR-like" substance therefore remains to be established.

Cell‐mediated anti‐tumor response in the RL♂ 1 system I. T nature, H‐2 Dd involvement and antigenic specificity of the effector cells

“…We found similar results with P8 15 (results not shown) as previously reported by Germain et al [24]. Moreover, an exclusive involvement of the product(s) of one region of the MHC has previously been observed in t h e interaction of anti-MSV or anti-FLV-CTL and syngeneic FMR' lymphomas [23]. It is remarkable, however, that the reactions directed against FMR' lymphomas of the same H-2d haplotype involved exclusively H-2Kd and not H-2Dd antigens [23].…”

“…Moreover, an exclusive involvement of the product(s) of one region of the MHC has previously been observed in t h e interaction of anti-MSV or anti-FLV-CTL and syngeneic FMR' lymphomas [23]. It is remarkable, however, that the reactions directed against FMR' lymphomas of the same H-2d haplotype involved exclusively H-2Kd and not H-2Dd antigens [23]. Regardless of its significance, this suggests that the functional association of H-2 and tumor antigens may depend on both the host H-2 [23] and the viral antigen (this study).…”

“…We therefore conclude that both the (B6 x C) and BALB/c effector cells were CTL. Table 7 showed that pre-incubation of RLd 1 (H-2d) with anti-H-2d antibodies abrogate the cytolysis by (B6 x c ) immune CTL (H-2bxd), whereas control anti-H-2b sera which specifically inhibited the lysis of B6 (H-2b) tumor cells by B6 anti-MSV CTL [23] were devoid of blocking activity. Furthermore, when "monospecific" antisera were used, it appeared that an anti-H-2Dd serum blocked strongly, while an antiserum directed against H-2Kd products was negative.…”

The Mouse Tumor Cell Lines EL4 and RMA Display Mosaic Expression of NK-Related and Certain Other Surface Molecules and Appear to Have a Common Origin

“…Remarkably, during the preparation of this paper, we found that two other tumor cell lines in our laboratory express the canonical EL4 V␤12 transcript. One is a line of the E&K1 tumor (77), and the other a line of MBL2, a tumor that has previously been reported to express Ly49 molecules (39), and which was derived at the same time and in the same laboratory as RBL5 (78). (A third line, E( G2 (81), was found to express a V␤12-containing receptor but this was associated with a V␤12-J␤2.1 transcript that had a distinct junctional sequence from that found in EL4 lines.)…”

Periodic loss of reactivity of a myeloma tumor with cytotoxic thymus-derived lymphocytes.

“…It is thus expected that syngeneic CTL responses to tumor-associated antigens on tumor cells are probably also subject to the same dual requirement for antigen plus H-2 products, and this expectation is supported by several observations (8)(9)(10). Accordingly, tumors that fail to react with syngeneic CTLs could be expected to lack either a tumor-specific antigen as has been described (11) or the appropriate H-2 products.…”